Project Summary/Abstract Humans have the ability to precisely sense the position, speed, and torque of their body parts. This sense is known as proprioception. In the many attempts to create human-mechatronic interactions there is still no robust, repeatable methodology to reflect proprioceptive information from a synthetic device onto the nervous system. The study presents a novel bi-directional neural communication paradigm ? called the Agonist- antagonist Myoneural Interface (AMI) ? for functional limb restoration after transtibial amputation. The AMI is a neural communication architecture comprised of two muscles ? an agonist and an antagonist ? surgically connected in series within the amputated residuum so that contraction of one muscle stretches the other. The AMI preserves important dynamic muscle relationships that exist within native anatomy, thereby allowing proprioceptive signals from mechanoreceptors within both muscles to be communicated to the central nervous system. It is hypothesized that surgically-constructed AMIs, created within the residuum during limb amputation, can afford an improved independent control of joint position and impedance in a multi-degree-of- freedom prosthesis while also reflecting proprioceptive sensation from each prosthetic joint onto the central nervous system. Following a prospective, case-control intervention model, we recruit healthy, active participants with transtibial amputations with and without the novel AMI surgical intervention. Each subject in the intervention group has an amputated residuum comprising two AMIs, enabling clinically translatable studies of myoelectric control of a prosthesis with actuated ankle and subtalar joints, and experimental demonstrations of closed-loop prosthetic joint torque control. Specific Aim 1 investigates if AMIs can improve control over voluntary prosthesis movement. Specific Aim 2 determines if AMIs can preserve involuntary (reflexive) gait behaviors during irregular terrain ambulation. Specific Aim 3 explores if an AMI construct can provide closed- loop joint torque control with somatotopically-matched force feedback. The research design includes the collection of electromyography, ultrasound, biomechanical (kinematic and kinetic), and psychometric data. Closed-loop joint torque control is provided through functional electrical stimulation. The extent of functional limb restoration enabled by the AMIs will be assessed using metric-based performance evaluations. Through insights on the capabilities of surgically-created bi-directional neural interfaces, the study provides a framework for integrating bionic systems with human physiology to improve the health, productivity, independence, and quality of life of persons with amputations.